The primary objective of this PO1 is to improve the treatment of patients with chronic myelogenous leukemia (CML). Hematopoietic cell transplantation is the treatment of choice for selected CML patients who have persistent or progressive disease following standard therapy. In either the autologous or allogeneic setting, providing specific and optimally potent anti-tumor therapy, such as the anti-PR1 specific cytolytic T cells (Projects 0006 and 0021), Herpes simplex virus-thymidine kinase (HSV-TK) transduced T cells (Project 0022) could result in major improvements in anti-tumor efficacy and safety. The use T cells primed against third party antigens may enhance engraftment without producing GVHD in recipients of haploidentical transplants (Projects 0006 and 00018). Production of genetically modified mesenchymal stem cells may allow targeted delivery of therapeutic cytokines into the tumor microenvironment (Project 0025). In the autologous transplant setting, the maximal eradication of tumor from the autograft, while maintaining or improving the rate of engraftment is critical if this source of hematopoietic support is to used effectively. The Good Manufacturing Practice (GMP)-Cell Therapy Laboratory Core, which is new to this PO1, will develop the clinical-scale procedures involving these strategies and provide the routine and manipulated hematopoietic cell grafts for the human clinical trials in Project 0006.The GMP-Cell Therapy Laboratory Core has the following specific aims: Aim 1) To generate anti-PR1 cytolytic T cells in upscale pre-clinical studies in collaboration with Project 0021. Aim 2) To optimize the herpes simplex virus thymidine kinase (HSV-TK) transduction procedure in upscale pre-clinical studies in collaboration with Project 0018. Aim 3) To generate anti-third party T lymphocytes in upscale pre-clinical studies in collaboration with Project 0018. Aim 4) To develop an plus mafosfamide CML purging regimen for autologous transplant patients. Aim 5) To optimize the clinical-scale procedures for the generation of autologous mesenchymal stem cells (MSCs) from CML patient bone marrow, which will then be transduced with the adeno-associated virus vectors for interferon alpha or MDA-7 in upscale pre-clinical studies in collaboration with Project 0025. Aim 6) To provide the routine hematopoietic cell products as well as the anti-PR1 cytolytic T cells, HSV-TK transduced T cells, anti-third party T lymphocytes, interferon alpha or MDA-7 transduced MSCs and imatinib plus mafosfamide purged autologous peripheral blood progenitor cells for the CML patients enrolled in the Project 0006 clinical studies.